SAN ANTONIO—Radiotherapy after breast-conserving surgery (BCS) will occur less frequently in the future and there is strong evidence that hypofractionated radiotherapy schedules should be “used frequently,” according to Jay R. Harris, MD, of the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School in Boston, MA. Dr Harris delivered a plenary lecture, “Critical Decision Making in Radiation Therapy,” at the 2015 San Antonio Breast Cancer Symposium.1
“Prior to 2005, it was widely thought that radiotherapy reduced local recurrence but did not influence survival,” Dr Harris said. “In 2005, an EBCTCG meta-analysis showed that radiotherapy after mastectomy or breast-conserving surgery [BCS] reduced local recurrence and improved survival.”
But the EBCTCG also postulated at that time—incorrectly—that for every 4 local recurrences avoided at 5 years, there would be 1 additional survivor at 15 years.
“The EBCTCG subsequently adopted ‘any first recurrence’—local or distant—as the primary endpoint for the effect of radiotherapy,” he noted.
The 2005 meta-analysis showed that radiotherapy proportionately reduced first recurrence “by about half,” and reduced breast cancer mortality by about one-sixth, Dr Harris said. “In many subsets of patients, however, the absolute benefit was quite small,” he emphasized.
Worse, the local recurrence and survival relationship didn’t hold up. “The survival benefit of radiotherapy is not mediated by its reduction in local recurrence,” he explained.
Reductions in local recurrence after BCS and radiation therapy are largely attributable to improvements in mammographic evaluation, improved pathologic evaluation, “and probably most importantly, the benefit seen with the addition of adjuvant systemic therapy,” he said.
“The new EBCTCG ratio: for every 1.5 first recurrences avoided at 10 years, there is an added survivor at 20 years,” he said.
In 2008, Dr Harris and colleagues were the first to show that local recurrence is linked primarily to the biologic subtype of tumors, rather than treatment approaches. “Five-year LR is 6% for triple-negative cancers and only about 1% for Luminal A cancers,” he noted.
They later showed that age is also a risk factor, albeit “a much lesser one,” with younger patients facing higher risks.
“For patients treated in the 1970s, the 5-year local recurrence rate was about 10%,” said Dr Harris. “Currently, the 5-year rate is about 2%. But ironically, in recent years, more patients are electing mastectomy.”
“Is breast radiotherapy needed after BCS? Radiotherapy reduces any first recurrence and mortality, but the absolute benefit is very small in some subgroups,” he said. “It is now time—past time—to find ways where radiotherapy can be safely omitted from patients’ treatment.”
One subset of patients who may be spared radiotherapy are older women diagnosed with small ER-positive, HER2-negative Luminal A subtype cancers. Dana-Farber has adopted a new protocol, he reported: women age 50 to 75 who are diagnosed with a T1N-Luminal A breast cancer (as assessed by Prosigna®) will be offered the option of hormone therapy alone.
Another important advance in breast cancer radiotherapy has been hypofractionation, Dr Harris said. It can bring treatment time from 6 weeks to 3 to 4 weeks. It was developed originally for convenience and cost improvements, and has been possible because of improvements in radiotherapy delivery and 3-dimensional conformal dose homogeneity.
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Hypofractionated radiotherapy “has been established as at least equal to conventional fractionation,” Dr Harris said. “Cosmetic results are clearly better and patient satisfaction is improved. There is uncertainty about its use in nodal radiotherapy.”
Which patients should undergo nodal radiotherapy is “a controversial issue and no clear consensus exists among experts,” Dr Harris said. Nodal radiotherapy can increase lymphedema by up to 8.4%, and increases radiation dose to heart and lung tissue, meaning “there will likely be more secondary cancers,” he concluded.
- Harris JR. Critical decision making in radiation therapy for breast cancer in 2015. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 9, 2015; San Antonio, TX.